Analgesic effects of diltiazem and verapamil after central and peripheral administration in the hot-plate test.
1. The analgesic effects of diltiazem and verapamil, both per se and together with morphine, were studied using subcutaneous (s.c.) and intracerebroventricular (i.c.v.) administrations, in the hot-plate test in mice. 2. The i.c.v. injection of verapamil (15-120 micrograms/mouse) and diltiazem (60-120 micrograms/mouse) induced dose-dependent analgesic effects. 3. The i.c.v. administration of verapamil (30-120 micrograms/mouse) and diltiazem (60-120 micrograms/mouse) significantly enhanced, in a dose-dependent way, the analgesic effects of morphine and produced a parallel displacement to the left of the morphine log dose-response line. 4. When these calcium channel blockers were administered subcutaneously at doses of 40 and 80 mg/kg, they exerted no analgesic actions, but dose-dependently potentiated the analgesic effects of morphine, producing a parallel shift to the left of the morphine log dose-response line. 5. These results suggest that inhibition of calcium entry through calcium channels induced by verapamil and diltiazem may play a role in analgesia development.
Del Pozo
E
E
Department of Pharmacology, School of Medicine, University of Granada, Spain.
Ruiz-García
C
C
Baeyens
J M
JM
D000700:Analgesics; D000818:Animals; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology*
D000700:Analgesics; D009020:Morphine; D014700:Verapamil; D004110:Diltiazem